IL12RB2 and ABCA1 genes are associated with susceptibility to radiation dermatitis.
OBJECTIVE
Severe acute radiation dermatitis is observed in approximately 5% to 10% of patients who receive whole-breast radiotherapy. Several factors, including treatment-related and patient-oriented factors, are involved in susceptibility to severe dermatitis. Genetic factors are also thought to be related to a patient's susceptibility to severe dermatitis. To elucidate genetic polymorphisms associated with a susceptibility to radiation-induced dermatitis, a large-scale single-nucleotide polymorphism (SNP) analysis using DNA samples from 156 patients with breast cancer was conducted.


METHODS
Patients were selected from more than 3,000 female patients with early breast cancer who received radiotherapy after undergoing breast-conserving surgery. The dermatitis group was defined as patients who developed dermatitis at a National Cancer Institute Common Toxicity Criteria grade of > or =2. For the SNP analysis, DNA samples from each patient were subjected to the genotyping of 3,144 SNPs covering 494 genes.


RESULTS
SNPs that mapped to two genes, ABCA1 and IL12RB2, were associated with radiation-induced dermatitis. In the ABCA1 gene, one of these SNPs was a nonsynonymous coding SNP causing R219K (P = 0.0065). As for the IL12RB2 gene, the strongest association was observed at SNP-K (rs3790568; P = 0.0013). Using polymorphisms of both genes, the probability of severe dermatitis was estimated for each combination of genotypes. These analyses showed that individuals carrying a combination of genotypes accounting for 14.7% of the Japanese population have the highest probability of developing radiation-induced dermatitis.


CONCLUSIONS
Our results shed light on the mechanisms responsible for radiation-induced dermatitis. These results may also contribute to the individualization of radiotherapy.
Isomura
Minoru
M
Genome Center, Japanese Foundation for Cancer Research, Japan.
Oya
Natsuo
N
Tachiiri
Seiji
S
Kaneyasu
Yuko
Y
Nishimura
Yasumasa
Y
Akimoto
Tetsuo
T
Hareyama
Masato
M
Sugita
Tadasi
T
Mitsuhashi
Norio
N
Yamashita
Takashi
T
Aoki
Masahiko
M
Sai
Heitetsu
H
Hirokawa
Yutaka
Y
Sakata
Koh-Ichi
K
Karasawa
Kumiko
K
Tomida
Akihiro
A
Tsuruo
Takashi
T
Miki
Yoshio
Y
Noda
Tetsuo
T
Hiraoka
Masahiro
M
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000150:complications* / Q000235:genetics* / Q000532:radiotherapy; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011855:Radiodermatitis / Q000235:genetics* / Q000532:radiotherapy; D053707:Receptors, Interleukin-12 / Q000235:genetics*; D012307:Risk Factors
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; C508439:IL12RB2 protein, human; D053707:Receptors, Interleukin-12